Surfaces that are resistance to protein adsorption and cell adhesion are critical for the development of biosensors with high specificity and biomaterials with superior compatibility. Currently, oligo(ethylene glycol) (OEG)- or polyethylene glycol (PEG)-based materials such as OEG self-assembling monolayers (SAMs) or poly(OEG methacrylate) are the most commonly used nonfouling materials. Recent studies attribute the nonfouling properties of OEG SAMs to their strong hydration capabilities and well-packed structures. Another commonly used nonfouling material is biomimetic phosphoryl choline (PC)-based materials containing PC headgroups, which are found in the outside layer of cell membranes. Polymers or surfaces modified with PC have been shown to reduce protein adsorption. Recently, applicants have shown that poly(sulfobetaine methacrylate) (polySBMA)-grafted surfaces have low protein adsorption when they are grafted from a surface via the surface-initiated atom transfer radical polymerization (ATRP) method.
Many applications of surface plasmon resonance (SPR) analysis require immobilization of antibodies on the SPR sensor. SPR sensors having immobilized antibodies have been used to detect analytes from complex biological solutions. The elimination of non-specific protein adsorption while maximizing the analyte signal is critical for SPR sensors. Different polymers, most of them with carboxylic acid groups, such as carboxymethylated dextran, carboxymethylated hyaluronic acid, polyacrylic acid and DL-polylactic acid, have been immobilized on the SPR gold surface. However, all these polymers are not protein resistant materials, which means they could adsorb non-specific proteins from complex biological solutions and mask the signal from analytes of interest. Usually, proteins such as BSA have been used to block a surface after the antibody immobilization, which can decrease non-specific binding, but can lead to low efficiency and some unwanted reactions for in vivo testing.
For biosensor or biomaterial applications, it is desirable to have a nonfouling surface or material as a background while presenting an abundance of functional groups for ligand immobilization. Mixed carboxylic (or amino) and hydroxyl-terminated oligo(ethylene glycol) (OEG) self-assembled monolayers (SAMs) or carboxymethyl dextran polymers are currently used in biosensor applications. Copolymers containing decoratable segments and nonfouling polyethylene glycol (PEG) polymers or low-fouling poly(hydroxyethyl methacrylate) or poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC) segments have been prepared to control cell and tissue responses. However, extra (or unreacted) functional groups can compromise the specificity of a sensor or the biocompatibility of a biomaterial.
Therefore, there is a need for a nonfouling biomaterial with active functional groups for protein or ligand immobilization. The present invention seeks to fulfill these needs and provides further related advantages.